Jenner's work is widely regarded as the foundation of immunology—despite the fact that he was neither the first to suggest that infection with cowpox conferred specific immunity to smallpox nor the first to attempt cowpox inoculation for this purpose. Jenner's work represented the first scientific attempt to control an infectious disease by the deliberate use of vaccination. Strictly speaking, he did not discover vaccination but was the first person to confer scientific status on the procedure and to pursue its scientific investigation.

Jenner worked in a rural society where most of his patients were farmers or worked on farms with cattle. In the 18th century Smallpox was considered to be the most deadly and persistent human pathogenic disease. The main treatment was by a method which had brought success to a Dutch physiologist, Jan Ingenhaus and was brought to England in 1721 by Lady Mary Wortly Montague, the wife of the British Ambassador to Turkey. This method was well known in eastern countries, and involved scratching the vein of a healthy person and pressing a small amount of matter, taken from a smallpox pustule of a person with a mild attack, into the wound. The risk of the treatment was that the patient often contracted the full disease, with fatal results.

In 1788 a wave of smallpox swept through Gloucestershire and during this outbreak Jenner observed that those of his patients who worked with cattle and had come in contact with the much milder disease called cowpox never came down with smallpox. Jenner needed a way of showing that his theory actually worked.
In 1796 Jenner conducted an experiment on one of his patients called James Phipps, an eight year old boy. After making two cuts in James’ arm, Jenner worked into them a small amount of cowpox puss. Although the boy had the normal reaction, of a slight fever, after several days, he soon was in good health. When, a few weeks later Jenner repeated the vaccination, using smallpox matter, the boy remained healthy. This is how Jenner’s vaccination treatment was born, named after the medical name for cowpox, vaccinia.

In 1798, Jenner published a small booklet entitled An Inquiry into the Causes and Effects of the Variolae Vaccinae, a disease discovered in some of the western counties of England, particularly Gloucestershire and Known by the Name of Cow Pox. Jenner decided to call this new procedure vaccination. The use of vaccination spread rapidly in England, and by the year 1800, it had also reached most European countries.

Late in the 19th century, the mortality from smallpox had declined, but the epidemics showed that the disease was still not under control. In the 1950s a number of control measures were implemented, and smallpox was eradicated in many areas in Europe and North America. The process of worldwide eradication of smallpox was set in motion when the World Health Assembly received a report in 1958 of the catastrophic consequences of smallpox in 63 countries. In 1967, a global campaign was begun under the guardianship of the World Health Organization and finally succeeded in the eradication of smallpox in 1977. Two-year old Rahima Banu is the last known person to be infected with natural-occurring smallpox reported om October 16, 1975 ( image below ) . On May 8, 1980, the World Health Assembly announced that the world was free of smallpox and recommended that all countries cease vaccination, 183 years after Edward Jenner first developed an inoculation.